Comparison of Volumetric Modulated Arc Therapy (VMAT) and Conventional Intensity-Modulated Radiotherapy (IMRT) for Locally Advanced Head and Neck Squamous Cell Carcinoma: A Retrospective Cohort Study.

Purpose This study examines the outcomes of locally advanced head and neck squamous cell carcinoma (HNSCC) following the adoption of conventional intensity-modulated radiotherapy (cIMRT) and volumetric-modulated arc therapy (VMAT) over a decade. The region under study has higher comorbidities associated with increased HNSCC incidence and poorer prognosis. Materials and methods A 10-year retrospective review of electronic medical records included 296 patients with stage III, IVA, and IVB HNSCC (American Joint Committee on Cancer, Seventh edition). Survival outcomes were compared between VMAT and cIMRT using Kaplan-Meier survival curves and adjusted for relevant demographic factors using Cox's proportional hazards model. Analysis was performed using R software (R Foundation, Vienna, Austria). Results The median age of the cohort was 63 years, comprising of 80% males. The oropharynx was the most common primary tumor site. 264 (89%) received 50Gy or higher dose radiation by either cIMRT (22%) or VMAT (67%). At five years, locoregional control (LC) and overall survival (OS) rates were 79.5% and 56.7%, respectively. VMAT showed a significant improvement in five-year OS (63.4% versus 43.8% for cIMRT, p=0.0023) but no significant difference in five-year LC (81% VMAT versus 74.5% cIMRT, p=0.17). Grade 3-4 acute toxicity was observed in 22% of patients. Conclusions VMAT and cIMRT demonstrated excellent LC in locally advanced HNSCC despite high comorbidity rates. Notably, VMAT was associated with significantly better OS compared to cIMRT. These outcomes surpass historical data, suggesting that VMAT technology may lead to improved patient outcomes. However, larger randomized controlled trials and dosimetric studies are needed to confirm these findings.

Digital Maturity as a Strategy for Advancing Patient Experience in US Hospitals.

Patient experience is globally recognized as an important indicator of health system performance, linked to health system quality and improving patient outcomes. Post COVID-19, health systems have embraced digital health and advanced digital transformation efforts; however, the relationship between digital health and patient experience outcomes is not well-documented. Using HCAHPS hospital survey data to measure patient experience, and HIMSS EMRAM Maturity Model data to measure digital maturity, a cross-sectional design using multivariate analyses examined the impact of digital maturity on patient experience in US hospitals. Our analysis shows that advanced digital maturity in US hospitals is associated with stronger patient experience outcomes, particularly relative to communication with nurses, doctors, and communication about medicines and therapies. The findings suggest that there are significant differences in patient experience associated with teaching versus nonteaching hospitals, urban versus rural hospitals. As hospitals advance and progress digital transformation initiatives, evidence to inform how transformation efforts can engage and advance patient experience will contribute to health system performance well into the future.

Real-world survival outcomes of immunotherapy for advanced non-small cell lung cancer: A single-center retrospective review.

BACKGROUND: Non-small cell lung cancer (NSCLC) is often diagnosed at an advanced stage. Clinical trials have demonstrated that first-line immunotherapy alone or in combination with chemotherapy improves overall survival. However, reports of survival outcomes in real-world settings are limited. We assessed survival in advanced NSCLC patients treated with immunotherapy alone or in combination with chemotherapy in first- or second-line at the Windsor Regional Cancer Program (WRCP) and compared it to existing literature. METHODS: We included patients diagnosed with stage IV NSCLC from January 2015 to December 2020 and treated with first-line chemoimmunotherapy (ChemoImmuno1), chemotherapy followed by immunotherapy (Chemo1), or immunotherapy followed by chemotherapy (Immno1) in our survival analysis. Patients with oncogene-addicted mutations were excluded. RESULTS: There were 160 patients of which 41.5% were female. Mean age was 68 years. Median overall survival from time of diagnosis was 474 days (95% CI: 249, 949) with an estimated 5-year survival of 11.1% (95% CI: 4.5, 21.3). Median OS in ChemoImmuno1 was 9.6 months, in Chemo1 was 19.2 months from time of diagnosis and 10.5 months from time of initiation of immunotherapy, and in Immuno1 was 18.4 months, respectively. Estimated survival at three years from time of diagnosis for ChemoImmuno1 was 17.6% and for Immuno1 was 17.9%. For Chemo1, from diagnosis it was 20.1% and from second-line therapy it was 15.4%. Survival outcomes were comparable to clinical trials and other studies. CONCLUSION: Real-world survival outcomes of immunotherapy for advanced NSCLC are comparable to the existing literature in this single center study.

Are we overtreating stage I triple-negative breast cancer in Ontario? A population-based retrospective epidemiological analysis using the ICES database.

Triple-negative breast cancer (TNBC) is associated with inferior outcomes. The use of adjuvant chemotherapy is the mainstay of treatment, and its efficacy was demonstrated to be correlated with tumor size. Different guidelines exist regarding chemotherapy in early-stage TNBC. This study uses ICES database to examine the outcomes of the use of adjuvant chemotherapy in stage I TNBC in Ontario stratified by tumor size. Records of TNBC patients diagnosed in 2012 to 2014 were collected from ICES database. Stage I patients were analyzed by tumor size: T1a (≤ 0.5 cm), T1b (> 0.5 cm and ≤ 1.0 cm), and T1c (> 1.0 cm and ≤ 2.0 cm). Kaplan-Meier curves, log-rank test statistic, and Cox's proportional hazard regression were used to compare differences in overall survival (OS) between chemotherapy and no-chemotherapy groups. Of 610 patients, 183 had tumor sizes ≤ 1 cm, representing stages T1aN0M0 and T1bN0M0, and 427 had tumors > 1 cm to 2 cm, representing stage T1cN0M0. Patients with tumors ≤ 1 cm who received chemotherapy did not have a significant difference in OS compared to the no-chemotherapy group (p = 0.41, hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.021-2.5). However, patients with tumor sizes > 1 cm to 2 cm who received chemotherapy demonstrated significantly better OS compared to those without (p = 0.023, HR = 0.40, 95% CI 0.16-0.86). Patients with TNBC stage T1cN0M0 should receive adjuvant chemotherapy. For TNBC tumors ≤ 1 cm, avoidance of chemotherapy can be considered. Prospective research should further investigate the efficacy of chemotherapy in TNBC stages T1a-bN0M0.Trial Registration University of Windsor REB#16-119.

Pattern of Treatment Initiation and Outcomes for Patients With Metastatic Non-small Cell Lung Cancer in Ontario.

INTRODUCTION: The impact of diagnosis and treatment delay on outcomes in advanced non-small cell lung carcinoma (NSCLC) is not well understood. In this study, we examined the effect of the length of time to the first chemotherapy treatment initiation and the other factors affecting overall survival. METHODS: This retrospective study used data from the Institute of Clinical Evaluative Sciences and identified 4520 patients in Ontario who were diagnosed with stage IV NSCLC between 2007 and 2016, treated using chemotherapy. We adjusted the analysis for location (rural vs urban), gender, distance from the nearest cancer center, first chemotherapy treatment used, income, and age.  Results: Type of the chemotherapy, length of time to the first treatment, and distance from the nearest cancer center had a statistically significant impact on survival. Paclitaxel was associated with decreased risk of death compared to vinorelbine (Hazard Ratio (HR)=0.835, 95%CI 0.753-0.925), gemcitabine (HR=0.916, 95%CI 0.998-0.826), and docetaxel (HR=0.771, 95%CI 0.994-0.513). Every additional 10 km distance from the nearest cancer center was associated with a 0.5% increased risk of death (HR=1.005, 95%CI 1.000-1.010). A longer time to the first treatment was associated with increased survival. In fact, every 10 days increase in wait time was associated with a 0.5% decrease in the risk of death (HR=0.995, 95%CI 0.993-0.998).  Conclusion: Chemotherapy treatment using paclitaxel and living closer to the cancer center is associated with better survival. A longer time between diagnosis and treatment leading to better survival could perhaps be explained by patients on the "sicker" end of the spectrum receiving treatment sooner.

Measuring Corrosion on Vehicles, in Real-Time, Using Digital Imaging and Analysis Techniques.

This research outlines a digital imaging method under development to systemize a rapid in-field corrosion evaluation measure, to evaluate and monitor the degree of corrosion on target corrosion-prone parts on light-duty vehicles. This procedure uses digital imaging to study and compare corrosion levels of 228 vehicles that were treated with aftermarket applications of corrosion prevention products versus 141 vehicles that were untreated. It introduces a Corrosion Index (CI) as a common measure. Single-factor and two-factor analysis of variance (ANOVA) of the digitally-based corrosion measurements show statistically significant correlations between CI and treatment (treated versus untreated), as well as CI, vehicle age, and treatment. The ANOVA results show that the aftermarket-treated vehicles have statistically significantly less corrosion than the untreated vehicles, demonstrating that digital image analysis is a viable method of measuring corrosion on corrosion-prone vehicle parts, offering the potential to monitor and track the performance/efficacy of aftermarket corrosion treatment in real-time.

Early-Stage Non-Small Cell Lung Cancer Stereotactic Body Radiation Therapy Outcomes in a Single Institution.

Introduction The gold standard treatment of stage I non-small cell lung cancer (NSCLC) is surgical resection. For medically inoperable patients, stereotactic body radiation therapy (SBRT) can provide comparable local control (LC) and overall survival (OS). The objectives of this study are to determine the three-year LC and OS for SBRT compared to early-stage NSCLC patients treated with alternative radiation modalities at our institution. Materials and methods This retrospective study included a total of 139 consecutive patients who were diagnosed with stage I (T1-2 N0 M0) NSCLC and treated with radiation therapy at our institution between 2015 and 2020. Patient demographics and clinical data were obtained from chart reviews. Treatment subgroups were: SBRT (48Gy/4 or 60Gy/8), hypofractionation (60Gy/15), conventional fractionation (60Gy/30 or 50Gy/20), and palliative radiation (20Gy/5, 30Gy/10, or 40Gy/15). Kaplan-Meier curves were plotted for LC and OS. We also performed Cox's proportional hazard regression analysis. Results The median patient age was 74 (range 52-91). The numbers of patients in each treatment subgroup were: SBRT (44), hypofractionation (78), conventional fractionation (8), and palliative (9). Differences in age, gender, and histopathological cell type between subgroups were not statistically significant. Metastatic progression was the most common outcome amongst treatment failures, followed by local recurrence and regional spread. Median post-treatment follow-up in months for each subgroup was: SBRT (20.2), hypofractionated (20.7), conventional fractionation (13.9), and palliative (14.4). Post-treatment three-year LC was found to be significantly better with SBRT (94%) versus hypofractionation (71%), conventional fractionation (80%), and palliative (71%). OS at three years were SBRT (67%), hypofractionation (59%), conventional fractionation (66%), and palliative (44%). As a whole, 72% (100/139) of patients had biopsy-proven NSCLC. Analysis showed biopsy status had no statistical significance with regards to LC or OS. Every 20 years of age had a 3.2x risk of death (95% CI: 1.425-7.268). Concerning the treatment modalities, there were significant differences for the hazard of death compared to SBRT: hypofractionation had 2.58x increased risk while palliative had 5.83x increased risk. The proportion of patients who experienced post-treatment radiation pneumonitis or dermatitis were: SBRT (7%, 2%), hypofractionation (8%, 3%), conventional fractionation (13%, 25%), and palliative (0%, 0%), respectively. No patients who experienced grade III or higher toxicities were observed as defined by Common Terminology Criteria for Adverse Events (CTCAE).  Conclusion Our experience confirms SBRT can provide durable three-year local control with a comparable rate of post-treatment complications versus other radiation modalities for early-stage NSCLC. SBRT appears to be non-inferior to hypofractionation with regards to three-year LC.

A prospective phase II clinical trial identifying the optimal regimen for carboplatin plus standard backbone of anthracycline and taxane-based chemotherapy in triple negative breast cancer.

Addition of platinums to combination chemotherapy for triple negative breast cancer (TNBC) has shown efficacy and is increasingly accepted in the clinic, yet optimal delivery is unknown. A prospective clinical trial with TNBC patients was conducted to determine the optimal chemotherapy regimen to deliver carboplatin with standard dose dense ACT. Tissue microarray was conducted to isolate markers indicative of response to treatment. 90 TNBC patients were enrolled onto our trial. The most successful version placed the carboplatin on the second and final paclitaxel treatment with liberal hematological parameters. Our final regimen had the lowest grade 3 or 4 toxicities, no delays, no dose reductions of carboplatin, and 32% reduction in paclitaxel doses. Stage I (AJCC7) patients did well with carboplatin-based chemotherapy with zero relapse rate. Reduction in protein levels of androgen receptor and PD-L1 were found to be potential indicators of patient relapse. We have optimized a protocol for the addition of carboplatin to standard of care chemotherapy in TNBC patients. Early data indicates reduced protein levels of androgen receptor and PD-L1 as indicators of response to treatment.Trial registration This trial was registered at Canadian Cancer Trials. http://www.canadiancancertrials.ca/.

Patient vital signs in relation to ICU admission in treatment of acute leukemia: a retrospective chart review.

OBJECTIVES: The objective of the current study was to investigate the relationship between changes in vital signs and intensive care unit (ICU) admission. Windsor Regional Hospital treats 15-20 new patients a year with acute leukemia. These patients are at increased risk of neutropenic fevers and admission to the ICU following induction chemotherapy. METHODS: Retrospective review examined the correlation between acute leukemia patient vitals and ICU admission. The analysis included 37 patients: 7 ICU versus 30 controls. Changes were compared to baseline over 24 hours prior to ICU admission or 5 days after the initiation of induction chemotherapy in the following vital signs: heart rate (HR), mean arterial pressure (MAP), temperature (T), respiratory rate (RR), and fraction of inspired oxygen (FiO2) required to maintain a stable oxygen saturation. RESULTS: RR and FiO2 demonstrated significant change over baseline leading up to ICU admission within the ICU group. T, HR and MAP did not demonstrate significant changes over time in either group. RR, FiO2 and HR were significantly higher in the ICU group at time zero compared with the control group. RR was recorded least frequently in the 24 hours leading up to ICU admission. DISCUSSION: Changes in RR and FiO2 predicted clinical deterioration requiring ICU admission in acute leukemia patients. This is consistent with the predominant reason for ICU admission which was respiratory failure. CONCLUSION: We present preliminary evidence to support enhanced monitoring of RR and FiO2 in acute leukemia patients following induction chemotherapy with early intervention if identified.

A bivariate autoregressive Poisson model and its application to asthma-related emergency room visits.

There are no gold standard methods that perform well in every situation when it comes to the analysis of multiple time series of counts. In this paper, we consider a positively correlated bivariate time series of counts and propose a parameter-driven Poisson regression model for its analysis. In our proposed model, we employ a latent autoregressive process, AR(p) to accommodate the temporal correlations in the two series. We compute the familiar maximum likelihood estimators of the model parameters and their standard errors via a Bayesian data cloning approach. We apply the model to the analysis of a bivariate time series arising from asthma-related visits to emergency rooms across the Canadian province of Ontario.

Neuroendocrine differentiation of prostate cancer leads to PSMA suppression.

Prostate-specific membrane antigen (PSMA) is overexpressed in most prostate adenocarcinoma (AdPC) cells and acts as a target for molecular imaging. However, some case reports indicate that PSMA-targeted imaging could be ineffectual for delineation of neuroendocrine (NE) prostate cancer (NEPC) lesions due to the suppression of the PSMA gene (FOLH1). These same reports suggest that targeting somatostatin receptor type 2 (SSTR2) could be an alternative diagnostic target for NEPC patients. This study evaluates the correlation between expression of FOLH1, NEPC marker genes and SSTR2. We evaluated the transcript abundance for FOLH1 and SSTR2 genes as well as NE markers across 909 tumors. A significant suppression of FOLH1 in NEPC patient samples and AdPC samples with high expression of NE marker genes was observed. We also investigated protein alterations of PSMA and SSTR2 in an NE-induced cell line derived by hormone depletion and lineage plasticity by loss of p53. PSMA is suppressed following NE induction and cellular plasticity in p53-deficient NEPC model. The PSMA-suppressed cells have more colony formation ability and resistance to enzalutamide treatment. Conversely, SSTR2 was only elevated following hormone depletion. In 18 NEPC patient-derived xenograft (PDX) models we find a significant suppression of FOLH1 and amplification of SSTR2 expression. Due to the observed FOLH1-supressed signature of NEPC, this study cautions on the reliability of using PMSA as a target for molecular imaging of NEPC. The observed elevation of SSTR2 in NEPC supports the possible ability of SSTR2-targeted imaging for follow-up imaging of low PSMA patients and monitoring for NEPC development.

Comparison of an Electronic and Paper-based Montreal Cognitive Assessment Tool.

This pilot study compared a novel electronic Montreal Cognitive Assessment (eMoCA) tool to the original paper-based MoCA. Potential participants were approached at primary care practices, a geriatric day hospital, and a university campus. Each of the 401 participants were randomly assigned to either the eMoCA (N=182) or MoCA (N=219). Scores were adjusted by self-reported demographic and health information using regression analysis. The difference in average scores (26.21±3.11 for the MoCA group and 24.84±4.21 for the eMoCA group) was found to be statistically significant. Controlling for the effect of potential covariate factors with regression analyses, the adjusted difference is -0.90 (95% confidence interval, -1.45 to -0.35). This difference may be due to factors related to use of the electronic device or software usability. However, the standardized, self-administered eMoCA may offer an opportunity for health systems to screen for early changes in cognitive function in primary care settings and offer greater access to assessment for rural or remote communities. Population-level research may be required to identify whether the score difference between test versions requires a downward adjustment to the eMoCA score taken as indicative of cognitive impairment.

Child restraint use in Canadian provinces with and without legislation in 2010.

OBJECTIVES: When used correctly, child safety seats reduce the risk of injury to a child passenger compared to seat belts. The objectives of this study are to (1) describe restraint use among Canadian children ages 4-8 years in 2010; (2) compare child safety seat use between provinces with new legislation (post-2006), old legislation (pre-2006), and without legislation; and (3) compare child safety seat use rates from 2006 to 2010. METHODS: Roadside observational surveys of child restraint use were performed in 2006 and 2010 using a nationally representative stratified sample. Proportions of restraint use, correct use (i.e., child safety seats and booster seats) in 4- to 8-year-old children was examined between 3 groups: provinces with new legislation (i.e., child safety seat legislation that included implementation of specific legislation for booster seat use for child passengers ages 4-8 years), old legislation, and no legislation. RESULTS: There were 4048 children observed as passengers in motor vehicles. In provinces with new legislation, 84 percent (95% confidence interval [CI], 72.2-90.8) of children were restrained compared to 94.9 percent (95% CI, 93.0-96.7) in provinces with old legislation, and 81.8 percent (95% CI, 77.3-86.3) in provinces without legislation. Correct use of child restraint was 54.1 percent (95% CI, 48.0-60.3) in provinces with new legislation, 29.5 percent (95% CI, 25.9-33.2) in provinces with old legislation, and 52.0 percent (43.0-61.0) in provinces without legislation in 2010. CONCLUSION: The findings from this study suggest that child safety seat legislation has an impact on restraint use in Canada. Despite the increase in rates of child safety seat use in provinces with new legislation and stable rates in provinces with old legislation, use rates remain low. Injury prevention strategies including further surveillance, interventions, and enforcement of restraint use in children are important to decrease motor vehicle related injury and death.

Monitoring binary outcomes using risk-adjusted charts: a comparative study.

Monitoring binary outcomes when evaluating health care performance has recently become common. Classical statistical methodologies such as cumulative sum (CUSUM) charts have been refined and used for this purpose. For instance, the risk-adjusted CUSUM chart (RA-CUSUM) for monitoring binary outcomes was proposed for monitoring 30-day mortality following cardiac surgery. The RA-CUSUM inherits optimality properties of the original CUSUM charts in the sense of signaling early when there is change. However, although the RA-CUSUM is a powerful monitoring tool, it will always eventually signal a change with probability 1 even when there is no real change. In other words, the probability of a type I error for the RA-CUSUM is 1. It also turns out that, because of the skewed distribution of the run lengths of the RA-CUSUM, the median is often well below the mean, and as a consequence more than half of all its false alarms occur before the designed average run length. In addition, when the change to be detected occurs at a later time in the series of observations being monitored, the rate of false alarms increases, and the RA-CUSUM may not be appropriate. Therefore, if the price of false alarms is high, it is preferable to use methods that control the rate of false alarms. In this paper, we propose alternative sequential curtailed and risk-adjusted charts that control the type I error rate in the context of monitoring 30-day mortality following cardiac surgery. We explore the merits of each of these methodologies in terms of average run lengths as well as in terms of type I error probabilities, and we compare them to the RA-CUSUM chart. We illustrate the methodologies by using data on monitoring performance of seven surgeons from a medical center.

Managing non-response rates for the National Child Safety Seat Survey in Canada.

BACKGROUND: Canada has a Road Safety Vision of having the safest roads in the world, yet vehicle crashes have remained the leading cause of death of Canadian children for a number of years. OBJECTIVES: Determine the influence of high rates of non-participation on the estimates for correct use of safety seats for child occupants in vehicles. Examine the impact of three different criteria for determining correct safety seat use on the estimates of correct use of safety seats for children in Canada. METHODS: A national child seat safety survey was conducted in 200 randomly selected sites across Canada that included both naturalistic observation of child seat safety use at intersections and a detailed vehicle inspection in nearby parking lots. Non-participation in the detailed parking lot study was high. This study reports on statistical methods for managing high rates of non-response and compared estimates of correct use using three different criteria. RESULTS AND CONCLUSIONS: Results revealed that high non-participation rates introduced bias into the raw estimates of correct safety seat use. Correct use estimates also varied substantially depending on which criterion (more stringent or less stringent) for correct use was applied in the analysis. When child age was the only criterion for correct use, estimates were higher than when more stringent criteria of child height and weight were applied to estimate rates of correct use. This study identifies the importance of managing high rates of non-response in safety seat observation studies using statistical techniques. Stringent criteria for correct use may provide more accurate estimates of the correct use of safety seats. Studies of child seat use in vehicles (using voluntary participation) may benefit from the use of naturalistic observation to capture non-participants' use of child occupant restraints, as it may more accurately estimate the rates of correct use in populations.

Children at risk: predictors of car safety seat misuse in Ontario.

When used correctly, child safety seats can reduce the risk of death and serious injury by 54% in toddlers and 71% in infants [National Highway Traffic Safety Administration (NHTSA), 2001. Traffic Safety Facts 2001. Children (DOT HS 809 471), U.S. Department of Transportation, Washington, DC]. The purpose of this study was to identify factors that predict correct use of car safety seats. The study was conducted in a large urban area in Southwestern Ontario and a small urban and rural area in Northern Ontario. Participants were 1263 caregivers who completed a self-report survey on their knowledge and use of car safety seats for their children (N=2199). Logistic regression analysis revealed that female caregivers, caregivers with higher levels of education, and caregivers who reported that finding information about the correct use of child safety seats was "difficult" were more likely to report correctly using car safety seats. The results also showed that children aged 7 months to 8 years old had substantially lower odds of being in the correct car safety seat compared to children aged 6 months or younger, or children aged 9 years or older. The high risk nature of misuse of child seats for infants and younger children may be an important cue to action for health professionals to develop comprehensive prevention strategies.